Estrogen Treatment for Transgender Women

Balancing the risks and benefits of estrogen options

Transgender women are women whose recorded sex at birth was male but whose gender identity is female. Transfeminine people represent a group that includes not just transgender women but also non-binary people who have a more feminine gender identity than the one that is expected for their recorded sex at birth. Many transgender people experience what is known as gender dysphoria—this is discomfort caused by people's bodies not matching their sense of identity.

Not every transgender person deals with their gender dysphoria in the same way. However, for many people, hormone therapy can help them feel more like themselves. For transmasculine people, this involves testosterone treatment. For transfeminine people, this usually involves a combination of testosterone blockers and estrogen treatment.

Testosterone blockers are a necessary part of estrogen treatment for transgender women because testosterone acts more strongly in the body than estrogen does. Therefore, in order for transfeminine people to experience the effects of estrogen treatment, they must block their testosterone. The most common medication used to block testosterone in transgender women is spironolactone or "spiro." Some women also have their testicles removed (orchiectomy) so that they can take a lower dose of estrogen and not need a testosterone blocker.

Effects of Estrogen Treatment

The purpose of estrogen treatment for transgender women is to cause physical changes that make the body more feminine. The combination of a testosterone blocker with estrogen can lead to the following types of desired changes in the body:

  • breast growth
  • decreased body and facial hair
  • redistribution of body fat
  • softening and smoothing of the skin
  • reduced acne

All of these are changes that can reduce gender dysphoria and improve quality of life. There are also some changes that occur that are less obvious. Some of these, like a reduction in testosterone, fewer penile erections, and a decline in blood pressure are generally considered to be positive changes. Others, like decreased sex drive and changes in cholesterol and other cardiovascular factors, may be less desirable.

The physical changes associated with estrogen treatment may start within a few months. However, changes can take two to three years to be fully realized. This is particularly true for breast growth. As many as two-thirds of transgender women are not satisfied with breast growth and may seek breast augmentation. Research suggests that this procedure depends on a number of factors including when hormone treatment is started and how fully testosterone is suppressed.

Methods for Taking Estrogen

Estrogen can be taken in a number of different ways. People receive estrogen through a pill, injection, patch, or even a topical cream. It's not just a matter of preference. The route by which people take estrogen affects some of the risks of estrogen treatment—estrogen is absorbed by the body differently depending on how you take it.

Much of the research on the risks of estrogen treatment focus on oral estrogens—those taken by mouth. What research has found is that oral estrogen seems to put women at an increased risk of a number of problematic side effects when compared to topical or injected estrogens. This is because of the effects of ingested estrogen on the liver when it passes through that organ during the process of digestion.

This is referred to as the hepatic first pass effect and it is not an issue for estrogen treatment that isn't taken in pill form. The hepatic first pass effect causes changes in a number of physiological markers that affect cardiovascular health. Changes are found in:

These changes may lead to an increase in blood clotting and reduced cardiovascular health. They are not seen as often, if at all, with non-oral estrogens. Therefore, non-oral estrogens may be a safer option for transgender women.

It is important to note that much of the research on the safety of estrogen treatment has been done in cisgender women taking oral contraceptives or hormone replacement therapy. This is potentially problematic as many of these treatments also contain progesterone, and the type of progesterone in these formulations has also been shown to affect the risk of cardiovascular disease. Transgender women do not usually receive progesterone treatment.

Types of Estrogens

In addition to the different routes of administration of estrogen treatment, there are also different types of estrogens used for treatment. These include:

  • oral 17B-estradiol
  • oral conjugated estrogens
  • 17B-Estradiol patch (usually replaced every three to five days)
  • estradiol valerate injection (every one to two weeks)
  • estradiol cypionate injection (every one to two weeks)

Endocrine society guidelines specifically suggest that oral ethinyl estradiol should not be used in transgender women. This is because oral ethinyl estradiol is the treatment most associated with thromboembolic events such as deep vein thrombosis, heart attack, pulmonary embolism, and stroke.

No matter what type of estrogen treatment is used, monitoring is important. The doctor who prescribes your estrogen should monitor the levels of estrogen in your blood.

The goal is to make certain you have similar levels of estrogen to premenopausal cisgender women, which is about 100 to 200 picogram/milliliter (pg/ml). Your doctor will also need to monitor the effects of your anti-androgen by checking your testosterone levels.

The testosterone levels should also be the same as for premenopausal cisgender women (less than 50 nanograms per deciliter). However, androgen levels that are too low may lead to depression and generally feeling less well.

Risks and Benefits

By Route of Administration

In general, topical or injected estrogen treatment is thought to be safer than oral treatment. This is because there is no hepatic first pass effect. Topical and injectable estrogens also need to be taken less often, which may make dealing with them easier. However, there are downsides to these options as well.

It is easier for people to maintain steady levels of estrogen on pills than with other forms of estrogen. This can affect how some women feel when taking hormone treatment. Since levels of estrogen peak and then decline with injections and transdermal (patch/cream) formulations, it can also be harder for doctors to figure out the right level to prescribe.

In addition, some people experience skin rashes and irritation from estrogen patches. Estrogen creams can be difficult to deal with for people who live with others who might be exposed by touching treated skin. Injections may require visiting the doctor regularly for people who are not comfortable giving them to themselves.

By Type of Estrogen

Oral ethinyl estradiol is not recommended for use in transgender women because it is associated with an increased risk of blood clots. Conjugated estrogens may also put women at higher risk than use of 17B-estradiol. Risk of thrombosis (blood clots) is particularly high for women who smoke. Therefore, it is recommended that smokers always be put on transdermal 17B-estradiol, if that is an option.

Treatment and Gender Surgery

Currently, most surgeons recommend that transgender women stop taking estrogen before they undergo gender affirmation surgery. This is because of the potentially increased risk for blood clots that is caused both by estrogen and by being inactive after surgery. However, it is unclear whether this recommendation is necessary for all women.

Transgender women who are considering surgery should discuss the risks and benefits of discontinuing their estrogen treatment with their surgeon. For some women, discontinuing estrogen is no big deal. For others, it can be extremely stressful and cause an increase in dysphoria. For such women, surgical concerns about blood clotting may be manageable using post-operative thromboprophylaxis. (This is a type of medical treatment that reduces the risk of clot formation.)

However, as individual risks depend on a number of factors including the type of estrogen, smoking status, type of surgery, and other health concerns. It is important that this be a collaborative conversation with your doctor. For some women, discontinuing estrogen treatment may be unavoidable. For others, risks may be managed in other ways.

A Word From Verywell

Transgender women taking estrogen treatment should be aware that they will need many of the same screening tests as cisgender women. In particular, they should follow the same screening guidelines for mammograms. This is because their breast cancer risk is much more similar to cisgender women than it is to cisgender men.

On the other hand, transgender women don't need to be screened for prostate cancer until after they turn 50. Prostate cancer appears to be quite rare in transgender women who have undergone a medical transition. This may be because of the reduced testosterone in their blood.

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